The bone marrow microenvironment in health and disease at a glance

Kumar, Rahul; Godavarthy, Parimala Sonika; Krause, Daniela

doi:10.1242/jcs.201707

Cited by 63 publications

(54 citation statements)

References 130 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mesenchymal stromal cells are a functional component of the BM niche with a key role in supporting HSPC homeostasis (Kfoury & Scadden, ). Aging is characterized by alterations in niche components and factors that can contribute to HSPC dysfunction and to the onset and progression of many hematological diseases (Kumar, Godavarthy, & Krause, ). Here, we conducted extensive characterization of ex vivo expanded BM‐derived MSC from young and geriatric healthy donors and identified signs of early senescence that encompassed accumulation of SA‐β‐Gal and lipofuscin, increased level of physical DNA damage and activation of DDR, and induction of a pro‐inflammatory secretory phenotype in aged MSC at early culture passage.…”

Section: Discussionmentioning

confidence: 99%

An early‐senescence state in aged mesenchymal stromal cells contributes to hematopoietic stem and progenitor cell clonogenic impairment through the activation of a pro‐inflammatory program

et al. 2019

View full text Add to dashboard Cite

Hematopoietic stem and progenitor cells (HSPC) reside in the bone marrow (BM) niche and serve as a reservoir for mature blood cells throughout life. Aging in the BM is characterized by low‐grade chronic inflammation that could contribute to the reduced functionality of aged HSPC. Mesenchymal stromal cells (MSC) in the BM support HSPC self‐renewal. However, changes in MSC function with age and the crosstalk between MSC and HSPC remain understudied. Here, we conducted an extensive characterization of senescence features in BM‐derived MSC from young and aged healthy donors. Aged MSC displayed an enlarged senescent‐like morphology, a delayed clonogenic potential and reduced proliferation ability when compared to younger counterparts. Of note, the observed proliferation delay was associated with increased levels of SA‐β‐galactosidase (SA‐β‐Gal) and lipofuscin in aged MSC at early passages and a modest but consistent accumulation of physical DNA damage and DNA damage response (DDR) activation. Consistent with the establishment of a senescence‐like state in aged MSC, we detected an increase in pro‐inflammatory senescence‐associated secretory phenotype (SASP) factors, both at the transcript and protein levels. Conversely, the immunomodulatory properties of aged MSC were significantly reduced. Importantly, exposure of young HSPC to factors secreted by aged MSC induced pro‐inflammatory genes in HSPC and impaired HSPC clonogenic potential in a SASP‐dependent manner. Altogether, our results reveal that BM‐derived MSC from aged healthy donors display features of senescence and that, during aging, MSC‐associated secretomes contribute to activate an inflammatory transcriptional program in HSPC that may ultimately impair their functionality.

show abstract

Section: Discussionmentioning

confidence: 99%

An early‐senescence state in aged mesenchymal stromal cells contributes to hematopoietic stem and progenitor cell clonogenic impairment through the activation of a pro‐inflammatory program

et al. 2019

View full text Add to dashboard Cite

show abstract

“…These niches can modulate different aspects of the hematopoiesis process, having the important role of cell–cell interaction and contact for the medullary microenvironment, as well as the production of soluble factors (cytokines and growth factors) and formation of an extracellular matrix that forms the supporting parenchyma [ 66 , 68 ]. All these elements act in different ways for the homeostasis of HSCs, as well as for the differentiation process of HSCs and progenitor hematopoietic cells and the mobilization of mature cells into peripheral blood [ 69 , 70 , 71 ]. However, the initiating factors that determine the differentiation process of HSCs are not entirely clear, and it is unknown how changes in Mg 2+ homeostasis can influence the bone marrow microenvironment.…”

Section: The Role Of Mg 2+ In Hematopoiesismentioning

confidence: 99%

A Review of the Action of Magnesium on Several Processes Involved in the Modulation of Hematopoiesis

Lima

Fock

2020

IJMS

View full text Add to dashboard Cite

Magnesium (Mg2+) is an essential mineral for the functioning and maintenance of the body. Disturbances in Mg2+ intracellular homeostasis result in cell-membrane modification, an increase in oxidative stress, alteration in the proliferation mechanism, differentiation, and apoptosis. Mg2+ deficiency often results in inflammation, with activation of inflammatory pathways and increased production of proinflammatory cytokines by immune cells. Immune cells and others that make up the blood system are from hematopoietic tissue in the bone marrow. The hematopoietic tissue is a tissue with high indices of renovation, and Mg2+ has a pivotal role in the cell replication process, as well as DNA and RNA synthesis. However, the impact of the intra- and extracellular disturbance of Mg2+ homeostasis on the hematopoietic tissue is little explored. This review deals specifically with the physiological requirements of Mg2+ on hematopoiesis, showing various studies related to the physiological requirements and the effects of deficiency or excess of this mineral on the hematopoiesis regulation, as well as on the specific process of erythropoiesis, granulopoiesis, lymphopoiesis, and thrombopoiesis. The literature selected includes studies in vitro, in animal models, and in humans, giving details about the impact that alterations of Mg2+ homeostasis can have on hematopoietic cells and hematopoietic tissue.

show abstract

“…Bone marrow microenvironment: The BM microenvironment is the domicile of hematopoietic stem cells (HSCs) as well as the malignant processes that develop in the BM [202]. The best characterized BM microenvironment is the niche that regulates HSCs [203].…”

Section: Bone Marrow Microenvironment and Hematopoiesismentioning

confidence: 99%

“…MSCs are a major constituents of HSC niche which is a highly complex and dynamic microenvironment of the BM [208]. They are de ined by a set of different markers such as: nestin, neural-glial antigen-2, leptin receptors, and paired related homeo box [202]. MSCs secrete HSC-supporting factors such as: CXCL-12, angiopoetin, and SCF/kit ligand [202].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

“…They are de ined by a set of different markers such as: nestin, neural-glial antigen-2, leptin receptors, and paired related homeo box [202]. MSCs secrete HSC-supporting factors such as: CXCL-12, angiopoetin, and SCF/kit ligand [202]. They synthesize and secrete multiple paracrine factors that are able to: affect migration of MSC, promote angiogenesis, and inhibit apoptosis [249].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

See 1 more Smart Citation

The beneficial effects of varicella zoster virus

Al-Anazi¹,

Wk²,

Al-Jasser³

2019

J Hematol Clin Res

View full text Add to dashboard Cite

Varicella zoster virus behaves differently from other herpes viruses as it differs from them in many aspects. Recently, there has been growing evidence on the benefi cial effects of the virus in immune compromised hosts and these effects are translated into prolongation of survival. The reported benefi cial effects of the virus include: (1) stimulation of bone marrow activity in patients with hematologic malignancies and bone marrow failure syndromes, (2) antitumor effects in various hematologic malignancies and solid tumors, and (3) association with graft versus host disease which has anticancer effects. Additionally, there are several reports on the safety of the live-attenuated even in severely immune suppressed individuals and on the emerging role of the virus in cancer immunotherapy. In this review, the following aspects of the virus will be thoroughly discussed: (1) new data on the genetic background, pathogenesis, vaccination, and new therapeutic modalities; (2) bone marrow microenvironment and hematopoiesis; (3) cells involved in the pathogenesis of the virus such as: mesenchymal stem cells, dendritic cells, natural killer cells, T-cells and mononuclear cells; (4) cellular proteins such as open reading frames, glycoproteins, promyelocytic leukemia protein, chaperons, and SUMOs; (5) extracellular vesicles, exosomes, and micro-RNAs; and (6) signaling pathways, cytokines, and interferons.

show abstract

The bone marrow microenvironment in health and disease at a glance

Cited by 63 publications

References 130 publications

An early‐senescence state in aged mesenchymal stromal cells contributes to hematopoietic stem and progenitor cell clonogenic impairment through the activation of a pro‐inflammatory program

An early‐senescence state in aged mesenchymal stromal cells contributes to hematopoietic stem and progenitor cell clonogenic impairment through the activation of a pro‐inflammatory program

A Review of the Action of Magnesium on Several Processes Involved in the Modulation of Hematopoiesis

The beneficial effects of varicella zoster virus

Contact Info

Product

Resources

About